Ethyl 4-oxo-1-piperidinecarboxylate → 1-Carbethoxy-4-hydroxy-4-[2-(4-methylphenylsulfanyl)phenyl]piperidine

HRID 1811353Notes

Reaction equation

[C:1]1([CH3:15])[CH:6]=[CH:5][C:4]([S:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2Br)=[CH:3][CH:2]=1.C([Li])CCC.[C:21]([N:26]1[CH2:31][CH2:30][C:29](=[O:32])[CH2:28][CH2:27]1)([O:23][CH2:24][CH3:25])=[O:22]>O1CCCC1>[C:21]([N:26]1[CH2:27][CH2:28][C:29]([OH:32])([C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[S:7][C:4]2[CH:5]=[CH:6][C:1]([CH3:15])=[CH:2][CH:3]=2)[CH2:30][CH2:31]1)([O:23][CH2:24][CH3:25])=[O:22]

Participants

Conditions

Temperature: -15 °C

Procedure

2-(4-tolylsulfanyl)-phenyl bromide (6.98 g, 25 mmol) was dissolved in heptanes (40 mL) and dry tetrahydrofuran (4.1 mL) and after 1.5 hrs the reaction mixture was cooled down to 0° C. under an atmosphere of nitrogen. n-Butyllithium in heptanes 2.7 M (9.8 mL, 26.5 mmol) was added at 0° C. and after 45 min the reaction mixture was cooled to −15° C. A solution of N-carbethoxy-4-piperidone (3.8 mL, 25 mmol) in tetrahydrofuran (15 mL) was added maintaining the temperature below −15° C. Once the addition was complete the reaction was allowed to warm to room temperature. The reaction was quenched with a dilute hydrogen chloride solution. A sample from the organic phase shows a ratio of 1-carbethoxy-4-hydroxy-4-[2-(4-methylphenylsulfanyl)phenyl]piperidine to 1-methyl-4-phenylsulfanyl-benzene of 28:58.

Workup

temperaturemaintaining the temperature below −15° C
additionOnce the addition
temperatureto warm to room temperature
customThe reaction was quenched with a dilute hydrogen chloride solution

Sources & evidence

ORD record: ord-9c01babdf1884d4e9108f3d30f86466e
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08362255B2

Reaction notes

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